Lyme disease is a major emerging infection in the United States, and has become a significant health issue in terms of public awareness, health care costs, and medical practice standards. Neurologic involvement is now recognized as the major morbidity of Lyme disease, but has not been studied in a systematic fashion. This Program Project has assembled an interdisciplinary team of investigators to study neurologic Lyme disease. They will utilize the clinical and laboratory resources of the Lyme Disease Center at Stony Brook. All components of this Program Project are linked by shared methodologies, conceptual frameworks, and common Cores. The three Clinical Projects will provide materials for the Pathogenesis Project: Project 1 will look at the role of host factors (the T cell response) and organism factors (neurotropism, antigenic variation). Project 2 will determine the frequency, correlates, and outcome of central nervous system invasion in early Lyme disease. Project 3 will characterize the neurobehavioral syndromes of chronic Lyme disease. Project 4 will study neurologic Lyme disease in children. The supporting Cores are: A) an Administrative Center Core; B) a Data Management Core; C) a Central Laboratory Core; D) a Neuropsychology Core. The primary scientific goals of this Program Project are 1) to identify and characterize prospectively the neurologic, neuropsychologic, and psychosocial manifestations of Lyme disease in children and adults; and 2) to identify pathogenetic mechanisms involved in neurologic Lyme disease. The secondary goals are 3) to characterize associated cerebrospinal fluid changes; and 4) to identify risk factors for poor outcome. This Program Project will support a structured interdisciplinary effort to study the neurologic aspects of Lyme disease. It will provide information to guide development of rational and cost-effective public health policy for this important infection.